Citations

Background and Purpose— Intravenous alteplase (tissue-type plasminogen activator) has been shown to be cost-effective because of savings in long-term disability. In October of 2005, an increased DRG payment to hospitals for alteplase-treated stroke patients was introduced. We sought to describe the trends in the cost of alteplase over time, in comparison to trends in hospital reimbursement in the United States. Methods— Using publicly available information on the Centers for Medicare and Medicaid Services (CMS) website ( www.cms.gov ), we obtained CMS quarterly payment amounts between January 1, 2005, and October 1, 2014, for alteplase, listed as alteplase recombinant, per mg. CMS payment amounts are the manufacturer’s average sales price+6% until April 2014, when it was lowered to +4.3%. Estimates for DRG base payments were calculated within the Medicare Provider and Analysis Review (MEDPAR) for fiscal years 2006 (DRG 559) and 2013 (MS DRGs 61, 62, and 63) as (DRG relative weights)×(standardized operating and capital amount). The consumer price index was also queried for all prescription drugs, urban areas, during the same study period as reference. Results— The CMS payment amount for alteplase per milligram was $30.50 in January 2005 and $64.30 in October 2014. Trends in the CMS payment amounts for alteplase increased by 111% between 2005 and 2014. The consumer price index for all prescription drugs increased by 30.2% in the same time frame. The base payment for alteplase-treated stroke admissions was $11 173 in 2006 and $12 064 in 2013, an 8% increase. Conclusions— We found a striking increase in the cost of alteplase over the last decade, with a 100 mg vial now with a CMS payment of ≈$6400, a >100% increase over 10 years. During the same time frame, the DRG base payment to hospitals increased by only 8%, and alteplase cost increased from 27% of the payment in 2006 to 53% in 2013. Researchers and stroke physicians should be aware of these changes in drug costs and their impact on cost-effectiveness analyses.

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long‐term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long‐term outcome. We identified 781 patients, median age 12 years, with 4,277 person‐years of follow‐up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event‐free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma‐glutamyltransferase, and aspartate aminotransferase‐to‐platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC–inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5‐0.9, and 0.7, 95% confidence interval 0.5‐0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long‐term outcome. Conclusion: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma‐glutamyltransferase, and aspartate aminotransferase‐to‐platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC–inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518–527).

Abstract Background: Epidemiologic associations of leukocyte telomere length (LTL) and pancreatic ductal adenocarcinoma (PDAC) have been inconsistent owing, in part, to variation in telomere length (TL) assessment across studies. To overcome this limitation and address concerns of potential reverse causation, we used carriage of telomere-related alleles to genetically predict TL and examined its association with PDAC. Methods: A case–control study of 1,500 PDAC cases and 1,500 controls, frequency-matched on age and sex was performed. Eight of nine polymorphisms previously associated with variation in LTL were analyzed. Genetic risk scores (GRS) consisting of the TL-related polymorphisms were computed as the number of long TL alleles carried by an individual scaled to published kilobase pairs of TL associated with each allele. Participants were further categorized on the basis of the number of short TL alleles they carry across all eight SNPs. Associations were examined in additive and dominant models using logistic regression to calculate ORs and 95% confidence intervals (CI). Results: In age- and sex-adjusted models, one short TL allele (rs10936599, T) was associated with reduced risk, whereas another short TL allele (rs2736100, A) was associated with increased risk, with per-allele ORs of 0.89 (95% CI, 0.79–0.99) and 1.13 (95% CI, 1.01–1.24), respectively. No association was observed with GRS or short TL allele counts, and no associations were observed in the dominant models. Conclusions: Findings suggest that genetically predicted short TL is not associated with PDAC risk. Impact: Common genetic determinants of short TL do not appear to influence PDAC risk. Cancer Epidemiol Biomarkers Prev; 26(6); 971–4. ©2017 AACR.

Prostate cancer is the most common malignancy of men in the United States. Small-cell carcinoma (SCC), which typically presents as an aggressive lung malignancy, is a rare diagnosis within the setting of prostate cancer pathology. Due to its limited prevalence, little information regarding the treatment and prognosis of this disease in large populations is available. To date our current knowledge base is largely limited to case reports and retrospective case reviews. The mainstay of treatment for this particular histology most often involves a multimodality approach utilizing chemotherapy in conjunction with radiation therapy, androgen deprivation therapy, or prostatectomy. Here we present the case of an elderly 89-year-old Caucasian male who was diagnosed with SCC of the prostate. Despite proceeding with a course of definitive radiotherapy, the patient experienced rapid progression of disease and ultimately elected to discontinue radiation therapy and receive hospice care.

Background Intracranial aneurysms ( IAs ), abdominal aortic aneurysms ( AAAs ), and thoracic aortic aneurysms ( TAAs ) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs , AAAs, and TAAs . Methods and Results We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study ( GWAS ) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA , AAA , and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA ‐, AAA ‐, and TAA ‐associated SNP s and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls ( IA ) and 4391 cases and 37 904 controls ( AAA ), and found nominally significant associations for IA risk locus 18q11 near RBBP 8 to AAA (odds ratio [ OR ]=1.11; P =4.1×10 −5 ) and for TAA risk locus 15q21 near FBN 1 to AAA ( OR =1.07; P =1.1×10 −3 ). Conclusions Although there was no evidence for polygenic overlap between IAs , AAAs , and TAAs , we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs . These two loci will require further replication.

ABSTRACT Introduction Despite recent advances in our knowledge and treatment strategies in Peyronie's Disease (PD), much remained unknown about this disease. Aim To provide a clinical framework and key guideline statements to assist clinicians in an evidence-based management of PD. Methods A systematic literature search was conducted to identify published literature relevant to PD. The search included all relevant articles published up to June 2015, including preclinical studies and published guidelines. References used in the text were assessed according to their level of evidence, and guideline recommendations were graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Owing to the paucity of larger series and randomized placebo-controlled trials with regard to surgical intervention, guideline statements are provided as clinical principle or expert opinion. Main Outcome Measures This literature was discussed at a panel meeting, and selected articles with the highest evidence available were used to create consensus guideline statements for the Fourth International Consultation on Sexual Medicine guidelines on PD. Results In addition to existing Third International Consultation on Sexual Medicine guidelines on PD, seven new summary recommendations were created. Conclusion A greater understanding of the scientific basis of PD is greatly needed to address our understanding of the pathophysiology, clinical epidemiology, psychosocial, and diagnostic assessment as well as treatment strategies.